Low Alkaline Phosphatase - Hypophosphatasia 



Is Low Alkaline Phosphatase Of Clinical Importance?



ALP enzyme- Discovered in 1923

Low ALP: Hypophosphatasia recognized in 1948 by Rathbun

ALP synthesized in: liver, bone, placenta and proximal convoluted tubule of the kidney.

Most cases diagnosed during childhood and adolescence.



Adult form: Less severe

 • softening of bones- osteomalacia

 • recurrent fractures of feet, thigh bones -> chronic pain

 • loss of secondary teeth prematurely

 • risk of joint pain and inflammation

 • nephrocalcinosis

 • CPPD

 • severe mobility/functional impairment

 • Neuropathy



ALP is critical for metabolizing 3 substrates:

 • Pyridoxal 5' phosphate: Impairs Vit. B6 transport across the plasma membrane into the CNS

 • Inorganic pyrophosphate: Inhibitor of bone mineralization

 • Phosphoethanolamine



Low ALP in adult population: also due to:

 • Malnutrition

 • Wilson's disease

 • hypothyroidism

 • Zinc deficiency

 • Vitamin C deficiency

 • Low phosphorus level

 • Pernicious anemia/B12 deficiency

 • blood collection with EDTA



Pathophysiology:

 • Activators of ALP → ↓ALP

 • Hypophosphatasia, ↓ALP 

	→ Low ALP -> PPi and Calcium accumulate

	→ PPi (inorganic pyrophosphate) blocks hydroxyapatite crystal formation causing poor bone mineralization



Symptoms of Low Alkaline Phosphatase:

 • Respiratory:

	- respiratory failure

 • Neurologic:

	- Increased intracranial pressure

	- Elevated Vit B6- neuropathy

 • Renal:

	- Renal failure

	- Nephrocalcinosis

	- Nephrolithiasis

 • Metabolic:

	- Hyperuricemia

	- Hyperlipidemia

	- Hypercalcemia

 • Skeletal:

	- Bone pain

	- Frequent fractures

 • Dental:

	- Premature loss of teeth

 • Muscular/Rheum:

	- Hypotonia

	- Pain (muscle/joint)

	- Waddling gait

	- Difficulty walking



Diagnosis of Low Alkaline Phosphatase:

 • Other causes of low ALP eliminated

 • Elevation of serum Pyridoxal 5' phosphate &/or

 • Elevation of urinary PEA



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